Our goal for human cancer is to understand the immunobiology of the tumor-host relationship. From correct perception of this relationship will come the advances necessary for immunological prevention, diagnosis or therapy of neoplastic disease. First, we must establish that tumor-specific antigens exist in human cancer. We plan to study a very prevalent form of human cancer, squamous cell carcinoma (SCC). To define characteristic tumor antigens in human squamous carcinoma, we will: establish a comprehensive serum bank containing serial serum specimens from many patients; establish new cell lines of human squamous carcinoma and corresponding normal fibroblasts from the same patients; preserve in our cell bank at early passage all new cultures; characterize as completely as possible all new cell lines and make them available for study by others; survey the autologous serum-tumor cell combinations with sensitive mixed hemadsorption and immune adherence assays for antibody reactive with cell surface antigens; and establish antibody specificity and antigen distribution by adsorption analysis. We refined our culture methodology such that our success rate for squamous carcinoma is now 20%. A total of 32 new SCC cell lines have been established from 26 patients. We have identified a characteristic membrane antigen phenotype of SCC lines that distinguishes these lines from other tumor types as well as the individual phenotypes which distinguish them from each other. SCC lines express: the epidermal cell-specific pemphigus antigen; blood group antigen corresponding to the donor blood type; HLA heavy chain and beta2 microglobulin. Reactivity with antibody to pemphigoid antigen (another epidermal antigen) is common with SCC lines but not with other cell types. SCC lines do not bind antibodies to HLA-DR antigens or to melanoma-associated antigens. A panel of monoclonal antibodies raised to UM-SCC-1 is being used to characterize the entire panel of UM-SCC lines. Autologous antibody reactivity is detectable in serum from many cell line donors. Absorption analysis of serum from one patient with high antibody levels defines an antigen present on both autologous SCC tumor lines but not on normal fibroblasts from this patient. Studies now under way are: continued characterization of this antigen including development of monoclonal antibodies against it as well as characterization of factors mediating growth promotion of SCC cells in vitro; sensitivity tests of SCC cells to chemotherapeutic agents in vitro; assessment of which SCC lines grow in nude mice; the expression of steroid hormone receptors by laryngeal carcinomas and the in vitro response of hormone receptor positive cells to antihormones.